Our goal is to explore a central mechanism by which cancer may arise from irradiation and other causes. In this scheme cancer results from an augmented or inappropriate expression of normal cellular genes (oncogenes) brought on by chemicals, radiation, viruses or aging. Some of these cellular cancer genes have been identified and characterized in retroviruses and others have been isolated by the DNA mediated 3T3 cell transformation technique. Highly specific molecularly cloned probes have been constructed that are now available for measuring expression of these oncogenes at the DNA and RNA level. By studying radiation and chemical induced tumors in RF mice, we plan to address 7 unanswered questions: (1) Do radiation induced neoplasms contain activated oncogenes?; (2) Are radiation induced oncogenes related to known viral or cellular oncogenes?; (3) Are radiation induced oncogenes the same in neoplasms from different target tissues?; (4) Do different carcinogens (chemical, viral, radiation) induce the same oncogenes in a given target tissue; (5) At what point in the neoplastic progression are the oncogenes expressed?; (6) Does radiation induce homologous oncogenes in different species; and (7) What is the mechanism of irradiation induced activation of oncogenes?